Title

Diagnostic accuracy of chromogranin A and calcitonin precursors measurements for the discrimination of ectopic ACTH secretion from Cushing's disease

Document Type

Journal Article

Publication Date

1-1-2009

Journal

Journal of Clinical Endocrinology and Metabolism

Volume

94

Issue

8

DOI

10.1210/jc.2009-0604

Abstract

Context: Inferior petrosal sinus sampling (IPSS) best discriminates between the two causes of ACTH-dependent Cushing's syndrome, Cushing's disease (CD) and ectopic ACTH secretion (EAS). However, when sampling is not available, adjunctive diagnostic tests might be helpful. Neuroendocrine tumors may secrete chromogranin A (CgA), calcitonin (CT), procalcitonin (ProCT), a fragment of the amino terminus of procalcitonin (NProCT), and/or ACTH. Objective: The aim of the study was to evaluate the ability of serum CgA, CT, ProCT, or NProCT values to distinguish CD from EAS. Design and Setting: We conducted a prospective pilot study at a clinical research center. Subjects and Methods: Serum ProCT, NProCT, and CgA were measured in six patients with occult EAS diagnosed by IPSS, 25 CD patients, and 11 patients with histologically proven EAS. Results: Nine EAS patients (53%) had at least one value above the reference range, including CgA alone (n = 4), ProCT alone (n = 3), CgA and ProCT (n = 1), and NProCT and ProCT (n = 1). Of nine (36%) CD patients with one or two abnormal values, seven had increased ProCT only, one had increased NProCT only, and one had increased CgA and ProCT. CgA had a positive predictive value of 83% and a negative predictive value of 70% for the diagnosis of EAS; other markers showed less discrimination. On pituitary magnetic resonance imaging, no EAS patient had an abnormality, whereas 21 of 25 patients with CD had a mass. Conclusion: These preliminary results suggest that an abnormal CgA and normal pituitary magnetic resonance imaging favor the diagnosis of EAS, but normal tumor markers do not exclude the diagnosis. Copyright © 2009 by The Endocrine Society.

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